April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Anti-IL-17 therapy reduces and reverses late-term corneal allograft rejection
Author Affiliations & Notes
  • Xiaotang Yin
    Eye Institute, Saint Louis University, St. Louis, MO
  • Jason Jarosz
    Eye Institute, Saint Louis University, St. Louis, MO
  • Patrick M Stuart
    Eye Institute, Saint Louis University, St. Louis, MO
  • Footnotes
    Commercial Relationships Xiaotang Yin, None; Jason Jarosz, None; Patrick Stuart, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5045. doi:
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      Xiaotang Yin, Jason Jarosz, Patrick M Stuart; Anti-IL-17 therapy reduces and reverses late-term corneal allograft rejection. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5045.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Corneal allograft rejection has been described as a Th1-mediated process involving IFN-γ production. However, recent evidence has also implicated IL-17 as being involved during acute corneal allograft responses. This study was designed to determine if IL-17 plays an identical or different role during late-term allorejection, which are corneal allografts that reject >50 days post-engraftment.

Methods: Mice were assessed for IL-17A, IFN-γ, and IL-6 during both acute and late term rejection. We then tested the ability of an anti-IL-17A neutralizing antibody to affect corneal responses during both acute and late-term rejection, to establish its role during those responses.

Results: While IL-17A was expressed at all time points measured, it peaked at the onset of late-term rejection. This peak was 15-30 times greater than during acute allorejection. When mice were treated with neutralizing anti-IL-17A right following corneal engraftment, our data supported previous studies indicating that it is involved in preventing acute corneal allograft rejection. In contrast, treatment of mice with the same neutralizing anti-IL-17A of graft acceptors at >45 days post-engraftment leads to significantly reduced corneal graft rejection. We went on to show that when corneal allografts that are undergoing early stage of late-term rejection are treated with anti-IL-17A, these grafts display a reversal of both opacity and neovascularization. We further identify the presence of CD4+ IL-17A+T cells and IL-17A+ F4/80+ macrophages within late-term rejecting corneal allografts.

Conclusions: These findings describe a new late-term murine model of corneal allograft rejection, which may have more direct relevance to clinical graft rejection. Using this model we present data which indicates that Th17 cells might be responsible for late-term allograft rejection and that therapeutic neutralization of IL-17A reverses this rejection thus suggesting that IL-17 is potentially an excellent target to reduce overall grafts loss of clinical PKP.

Keywords: 480 cornea: basic science • 741 transplantation • 555 immunomodulation/immunoregulation  

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